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Simulation of the Ras/cAMP/PKA pathway in budding yeast highlights the establishment of stable oscillatory states

Paper ID Volume ID Publish Year Pages File Format Full-Text
14588 1232 2012 9 PDF Available
Title
Simulation of the Ras/cAMP/PKA pathway in budding yeast highlights the establishment of stable oscillatory states
Abstract

In the yeast Saccharomyces cerevisiae, the Ras/cAMP/PKA pathway plays a major role in the regulation of metabolism, stress resistance and cell cycle progression. We extend here a mechanistic model of the Ras/cAMP/PKA pathway that we previously defined by describing the molecular interactions and post-translational modifications of proteins, and perform a computational analysis to investigate the dynamical behaviors of the components of this pathway, regulated by different control mechanisms. We carry out stochastic simulations to consider, in particular, the effect of the negative feedback loops on the activity of both Ira2 (a Ras-GAP) and Cdc25 (a Ras-GEF) proteins. Our results show that stable oscillatory regimes for the dynamics of cAMP can be obtained only through the activation of these feedback mechanisms, and when the amount of Cdc25 is within a specific range. In addition, we highlight that the levels of guanine nucleotides pools are able to regulate the pathway, by influencing the transition between stable steady states and oscillatory regimes.

Keywords
Mechanistic modeling; Stochastic simulation; Oscillation; cAMP; Ira2; Cdc25; Guanine nucleotide
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biotechnology Advances - Volume 30, Issue 1, January–February 2012, Pages 99–107
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us